Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat.

Kempson, Stephen A.; Colón‐Otero, Gerardo; Ou, Shiyi; Turner, Stephen T.; Douša, Thomas P.

doi:10.1172/jci110163

Cited by 120 publications

(57 citation statements)

References 35 publications

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“…A pharmacologic dose of NAM inhibits renal and intestinal Na/Pi transport activity in normal rats. 15,16 In those animals, cellular NAD levels are increased in inverse proportion to Na/Pi transport activity. 16 Indeed, we showed that NaPi-II protein levels were markedly decreased and NAD concentrations were increased at kidney in PH animals, suggesting that the effects were similar to those in NAM-treated animals.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 In those animals, cellular NAD levels are increased in inverse proportion to Na/Pi transport activity. 16 Indeed, we showed that NaPi-II protein levels were markedly decreased and NAD concentrations were increased at kidney in PH animals, suggesting that the effects were similar to those in NAM-treated animals. NAM concentrations in the urine of PH rats, however, were approximately 10 times lower than those in the rats administered a pharmacologic dose of NAM (1 g/kg body weight; Supplemental Figure 1).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…[15][16][17] Administration of NAM to rats produces a specific dose-dependent inhibition of Na/Pi transport across the renal brush-border membrane (BBM) and an increase in urinary Pi excretion. 16,17 NAM suppresses hyperphosphatemia in hemodialysis patients. 18 Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first ratelimiting step in converting NAM to NAD, 19,20 which is essential for cellular metabolism, energy production, and DNA repair.…”

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confidence: 99%

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Hepatectomy-Related Hypophosphatemia

Nomura

Tatsumi

Miyagawa

et al. 2014

Journal of the American Society of Nephrology

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Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na + -dependent phosphate (Pi) uptake decreased by 50%-60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na + -dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Hepatectomy-Related Hypophosphatemia

Nomura

Tatsumi

Miyagawa

et al. 2014

Journal of the American Society of Nephrology

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“…The rate of Na'-H' exchange was determined by using a rapid filtration technique (23,24), basically as described by Frieberg et al (19), except that we employed BBMVs prepared by the calcium precipitation method, and that the pH of the intravesicular medium was pH 6.0 instead of 5.5. In the experiments when Na+-H+ exchange across the BBM was measured, BBMVs were prepared as in other solute uptake studies (18)(19)(20), but were preloaded (13) (12)(13)(14)(15). Because the Na+-H+ antiport in the renal BBM is specifically blocked by amiloride (17), the 22Na' uptake at pH gradient condition (pHi < pHO) was always measured simultaneously with and without addition of I mM amiloride, the maximum inhibitory concentration of the compound (17).…”

Section: Methodsmentioning

confidence: 99%

Administration of atrial natriuretic factor inhibits sodium-coupled transport in proximal tubules.

Hammond

Yusufi²,

Knox³

et al. 1985

J. Clin. Invest.

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118

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The newly discovered peptides extracted from cardiac atria, atrial natriuretic factors (ANFs), when administered parenterally cause renal hemodynamic changes and natriuresis. The nephron sites and cellular mechanism accounting for profound increase in Na' excretion in response to ANFs are not yet clarified. In the present study we investigated whether synthetic ANF peptide alters the reabsorption of Na' and reabsorption of solutes cotransported with Na' in the proximal tubules of rats.Synthetic ANF peptide consisting of 26 amino acids, 4 ag/kg body wt/h, or vehicle in controls, was infused to surgically thyroparathyroidectomized anesthetized rats. After determination of the fractional excretion (FE) of electrolytes (Na', K+, P,, Ca2+, Mg2+, HCO3), the kidneys were removed and luminal brush border membrane vesicles (BBMVs) were prepared from renal cortex. Solute transport was measured in BBMVs by rapid filtration techniques. Infusion of ANF peptide increased FENa, FEp,, and FEHCO,; but FEc., FEK, and FEMg were not changed. The increase in FENa was significantly correlated, on the one hand, with increase of FEp, (r = 0.9, n = 7; P < 0.01) and with increase of FEHCO3 (r = 0.89, n = 7; P < 0.01). On the other hand, FEN. did not correlate with FEK, FEca, or with FEM.. The Na+ gradient-dependent uptake of Pi by BBMVs prepared from renal cortex of rats receiving ANF infusion was significantly (P < 0.05) decreased (-25%), whereas the Na+ gradient-dependent uptake of L-13H]proline and of D-I3Higlucose or the diffusional uptake of 22Na+ were not changed. ANF-elicited change in FEn showed a close inverse correlation with decrease of Na+-dependent Pi uptake by BBMVs isolated from infused rats (r = 0.99, n = 7; P < 0.001). Direct addition of ANF to BBMVs in vitro did not change the Na+ gradient-dependent Pi uptake. In rats infused with ANF, the rate of amiloride-sensitive Na+-H+ exchange across the brush border membrane (BBM) was significantly (P < 0.05) decreased (-40%), whereas the diffusional 22Na+ uptake (0.5 min) and the equilibrium (120 min) uptake of 22Na+ were not changed. The inhibition of Na+-H+ exchange after ANF was likely due to alteration of the BBM antiporter itself, in that the H+ conductance of BBMVs was not increased. We conclude that synthetic ANF (a) decreases tubular Na+ reabsorption linked to reabsorption of HCO3 in proximal tubules, and (b) inhibits proximal tubular reabsorption of Pi coupled to Na+ reabsorption, independent of secretion and/or

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The interaction between gluconeogenic metabolism and accumulation of phosphate by chick kidney tubule cells

Grahn

Parveen

Butterworth

1985

Cell Biochemistry & Function

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Pyruvate promotes both phosphate uptake and glucose synthesis by isolated chick kidney proximal tubule cells. 3-Mercaptopicolinate inhibits both glucose synthesis and the promoted phosphate accumulation to the same extent. Glycerol also stimulates glucose synthesis, but does not affect phosphate accumulation. Oxygen utilization by the tissue is slightly stimulated by glycerol and pyruvate, but the enhancement of uptake by pyruvate is unlikely to result from raised cellular oxidative phosphorylation. The action of pyruvate is not a direct effect on the phosphate transporter, or on the transport of phosphate across the basolateral membrane, but entails an obligatory flux to triose phosphate.

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Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat.

Cited by 120 publications

References 35 publications

Hepatectomy-Related Hypophosphatemia

Hepatectomy-Related Hypophosphatemia

Administration of atrial natriuretic factor inhibits sodium-coupled transport in proximal tubules.

The interaction between gluconeogenic metabolism and accumulation of phosphate by chick kidney tubule cells

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